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| Status |
Public on Jun 29, 2019 |
| Title |
Differential c-Kit expression identifies two subsets of ILC2s with IL-17 producing capabilities that may contribute to IL-17 mediated pathologies |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Group 2 innate lymphoid cells (ILC2s) are linked to type 2 immune diseases but can also molecularly change phenotype and provide type 1 immunity towards pathogens. Here we identify an ILC2 subset which can convert into IL-17 producing NKp44‒ ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation which exhibit ILC3 features, including RORγt, which enables the conversion into IL-17 producing cells in response to IL-1β and IL-23. We also report a novel but critical role for TGF-β in promoting the conversion of c-kit‒ ILC2s into RORγt expressing c-Kit+ ILC2s by inducing the upregulation of IL23R, CCR6 and KIT mRNA in these cells. This switch was dependent on RORγt and down-regulation of GATA-3. IL-4 was able to reverse this event supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance as a subset of RORγt+ ILC2s express the skin homing receptor CCR10 and the frequencies of IL-17‒producing ILC3s are increased at the expense of ILC2s within the lesional skin of psoriatic patients compared to healthy individuals.
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| Overall design |
c-kit‒ and c-Kit+ ILC2 subsets purified from PBMC by flow cytometry were stimulated with different combinations of IL-1β, IL-23 and TGF-β to induce IL-17A production
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| Contributor(s) |
Bernink JH, Teunissen MB, Volckmann R, Koster J, Spits H |
| Citation missing |
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| |
| Submission date |
Apr 02, 2019 |
| Last update date |
Jul 01, 2019 |
| Contact name |
Richard Volckmann |
| E-mail(s) |
r.volckmann@amsterdamumc.nl
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| Organization name |
Academic Medical Centre, University of Amsterdam
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| Department |
Department of Oncogenomics
|
| Street address |
P.O. Box 22700
|
| City |
Amsterdam |
| ZIP/Postal code |
1100DE |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL24324 |
[Clariom_S_Human_HT] Affymetrix Clariom S Assay HT, Human (Includes Pico Assay) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA530567 |
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